Automated sample diagnostic analyzer and method for its operation

ABSTRACT

Automated analyzer ( 2000 ) comprising a housing ( 2010, 3010 ), a robotic arm comprising an end effector ( 2360 ), the end effector ( 2360 ) comprising a body ( 2320 ) rotatably connected to an articulating arm and first ( 2363   a ) and second fingers ( 2363   b ) coupled to the body ( 2362 ) and being moveable relative to each other in a first direction, each of the fingers ( 2363   a, b ) having an engagement feature ( 2361 ) projecting inwardly from each of the first and second fingers ( 2363   a, b ) and toward the other of the first and second fingers ( 2363   a, b ). The automated analyzer ( 2000 ) further comprises a shuttle platform ( 2030 ) for receiving a shuttle ( 2030 ) carrying sample containers ( 03 ), the containers carrying sample ( 03 ) to be evaluated by the analyzer ( 2000 ) and the shuttle platform ( 2030 ) comprising a jaw assembly that engages the bottom portion of the sample containers when the jaw assembly is in the closed position.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a national phase entry under 35 U.S.C. § 371of International Application No. PCT/US2017/018346, filed Feb. 17, 2017,published in English, which application claims the benefit of the filingdate of U.S. Provisional Application No. 62/326,259, filed Apr. 22,2016, the disclosure of which is hereby incorporated herein byreference.

BACKGROUND OF THE INVENTION

Diagnostic testing of biological samples is instrumental in the healthcare industry's efforts to quickly and effectively diagnose and treatdisease. Clinical laboratories that perform such diagnostic testingalready receive hundreds or thousands of samples on a daily basis withan ever increasing demand. The challenge of managing such largequantities of samples has been assisted by the automation of sampleanalysis. Automated sample analysis is typically performed by automatedanalyzers that are commonly self-contained systems which performmultistep processes on the biological samples to obtain diagnosticresults.

Several current automated clinical analyzers offer a user an array ofautomated tests or assays that can be performed on a provided sample.Additionally, when samples arrive at the laboratory, they are often notready for analysis. In order to prepare a sample for testing with anautomated analyzer, a lab technician typically transfers an aliquot ofthe sample from a primary container, as received by the laboratory, to asecondary container which is amenable to the analyzer. In addition, thetechnician typically must know what tests are to be performed on thesample so that the technician can select a test specific reagent ordiluent to be paired with the sample. This can be time consuming and canlead to operator error and exposure to communicable diseases.

Pre-analytical systems meant to help prepare a sample for analysis andfurther remove the operator from the workflow between the laboratory'sreceipt of a sample and the analyzer's test results also exist. However,many of these systems still require significant technician involvement,such as: prior to loading samples in the pre-analytical system; afterthe samples have been prepared by the pre-analytical system; and afterthe analyzers have completed analysis.

For example, some pre-analytical systems may automatically transfer analiquot of sample from a first container to a second container. However,such systems often require a technician to manually match identificationcodes of the first and second containers prior to loading them into thesystem, which can be time consuming and is prone to error.

In addition, many of these systems are not capable of being integratedwith one or more analyzers, and, conversely, the analyzers are notcapable of being integrated with such systems. In this regard, atechnician must be present to manually transfer the samples from thepre-analytical system to an analyzer and from the analyzer to a storagelocation once analysis is complete. This requires skilled labor toperform menial tasks and can create distractions in that the technicianmust be ever mindful of the progress of the samples within thepre-analytical system and analyzer so that the technician is prepared totransfer samples when ready in order to minimize downtime.

Moreover, current pre-analytical systems generally prepare samples atdifferent rates than the analyzers evaluate such samples and thisfurther complicates the integration between pre-analytical systems andanalyzers. In this regard, a technician may be required to continuouslykeep track of samples prepared by the pre-analytical system until a fullbatch of samples is accumulated for manual transfer to an analyzer.Alternatively, technicians may transfer partial batches to an analyzer,which can reduce the analyzer's productivity.

Thus, while current automated pre-analytical systems and analyzers arebeneficial to the clinical laboratory, there is room for betterintegration and automation of various systems.

BRIEF SUMMARY OF THE INVENTION

The present disclosure describes devices, systems, and methods forsample processing and analysis. In particular, an analyzer that isincluded in a high-throughput system is described. In one embodiment,the high-throughput system may also include a second analyzer and apre-analytical system integrated with both first and second analyzers.These components (i.e., analyzers and pre-analytical system) are modularand are capable of being integrated in several different configurationsto conform to a particular laboratory's diagnostic needs.

The particular analyzer described herein generally has multiple decks orlevels in a vertical arrangement. One deck may store consumables forvarious assays and may house consumable waste which includes liquidwaste. In one embodiment, enough consumables can be stored in theanalyzer to allow it to operate 24 hours straight without reloading thesystem. This deck may also include detectors for detecting an analyte,such as a DNA target.

Another deck may include multiple processing modules arrangedside-by-side. Each one of these processing modules may be similarlyconfigured in terms of their structure and functions. In one embodiment,each processing module is capable of performing a wide array of assaysso that each processing module can run a different assay concurrentlywith assays being run on other processing modules. In this regard, eachprocessing module can be automatically designated and redesignated toperform any number of assays depending on the processing needs at aparticular point in time. For example, each processing module may becapable of performing any of a first, second or third assay, but a firstprocessing module may be designated to perform the first assay, a secondprocessing module the second assay, and a third processing module thethird assay where each assay is different. However, when those assaysare completed, any one of the processing modules can be automaticallyredesignated to perform a different assay, so that each of the first,second, and third processing module are running the same assaysimultaneously, for example. As such, the analyzer is flexible toaccommodate real-time needs provided sufficient consumables for aparticular assay are inventoried within its housing.

Each processing module may have a multichannel pipettor with multiplepipette channels associated with it. In addition, the analyzer may havean inventory robot that periodically performs an inventory inspection todetermine if sufficient consumables are available, moves consumablesback and forth between the inventor to the processing deck, and movessample containers back and forth between the pre-analytical system andthe analyzer. More particularly, the inventory robot includes anelectronic or optoelectronic inventory scanner and an end-effector thatis configured to handle a variety of consumables including a samplecontainer shuttle, an amplification cartridge, a liquid reagent plate, adry reagent plate, and a sample processing plate.

BRIEF DESCRIPTION OF THE DRAWINGS

The features, aspects, and advantages of the present invention willbecome better understood with regard to the following description,appended claims, and accompanying drawings in which:

FIG. 1 is a front perspective view of a high-throughput diagnosticsystem according to one embodiment of the present disclosure.

FIG. 2 is a front partially transparent view of a first analyzer of thesystem of FIG. 1 according to one embodiment of the present disclosureand absent its external housing and certain components therein.

FIG. 3 front perspective view of the analyzer of FIG. 2.

FIG. 4A is a perspective view of a first pipette tip according to oneembodiment of the present disclosure.

FIG. 4B is a perspective view of a second pipette tip according to oneembodiment of the present disclosure.

FIG. 5 is perspective view of a sample container shuttle according toone embodiment of the present disclosure.

FIG. 6 is a perspective view of processing plate according to oneembodiment of the present disclosure.

FIG. 7 is a perspective view of a dry reagent plate according to oneembodiment of the present disclosure.

FIG. 8 is a perspective view of a liquid reagent plate according to oneembodiment of the present disclosure.

FIG. 9 is a top view of an amplification cartridge according to oneembodiment of the present disclosure.

FIG. 10A is a rear perspective view of a consumable repository accordingto one embodiment of the present disclosure.

FIG. 10B is a rear perspective view of a waste repository according toone embodiment of the present disclosure.

FIG. 10C is a front perspective view of a pipette tip drawer accordingto one embodiment of the present disclosure.

FIG. 11A is a top view of a processing deck according to one embodimentof the present disclosure.

FIG. 11B is a top view of a first processing module of the processingdeck of FIG. 11A according to one embodiment of the present disclosure.

FIG. 11C is a schematic view of a sample container being engaged by asample container retention assembly of the processing deck of FIG. 11A.

FIG. 12A is a front perspective view of an extractor of the processingmodule of FIG. 11B according to one embodiment of the presentdisclosure.

FIG. 12B is a top view of the extractor of FIG. 12A.

FIG. 12C is a perspective view of alternative embodiments of anextractor and processing plate.

FIG. 12D is a side view of the extractor and processing plate of FIG.12C.

FIG. 12E is a partial perspective view of a processing deck of thesystem of FIG. 1 including the extractor and processing plate of FIG.12C.

FIG. 13A is a front perspective view of an inventory robot according toan embodiment of the present disclosure.

FIG. 13B is an end-effector of the robot of FIG. 13A according to oneembodiment of the present disclosure.

FIG. 13C is an amplification cartridge engagement member of the endeffector of FIG. 13B.

FIG. 13D is a side view of the engagement member of FIG. 13C engaging anamplification cartridge.

FIG. 14A is a front view of a liquid handling assembly according to anembodiment of the present disclosure.

FIG. 14B is a front perspective view of a multichannel pipettor of theliquid handling assembly of FIG. 14A.

FIG. 15 is a block diagram of an exemplary architecture of a computingsystem involving the analyzer of FIG. 2 including example componentssuitable for implementing methodologies of the present disclosure.

FIG. 16 is a flow diagram of a method of using the analyzer of FIG. 2according to one embodiment of the present disclosure.

FIG. 17A is a front view of an analyzer according to another embodimentof the present disclosure.

FIG. 17B is a front perspective view of the analyzer of FIG. 17A.

FIG. 17C is a side view of the analyzer of FIG. 17A.

FIG. 18A is a front perspective view of the analyzer of FIG. 17Aincluding an external skin but absent front doors.

FIG. 18B is a partial front perspective view of the analyzer of FIG. 18Aincluding a single front door.

FIG. 18C is a perspective view of moveable consumable inventory.

DETAILED DESCRIPTION

As used herein, the terms “about,” “generally,” and “substantially” areintended to mean that slight deviations from absolute are includedwithin the scope of the term so modified. Also when referring tospecific directions, such as left, right, front, back, up and down, inthe following discussion, it should be understood that such directionsare described with regard to the perspective of a user facing the belowdescribed system during exemplary operation.

FIG. 1 depicts a high-throughput system 00 which includes a firstanalyzer 2000, a second analyzer 4000 and a pre-analytical system 10,such as the pre-analytical system described in U.S. ProvisionalApplication 62/296,349 (“the '349 Application”), the disclosure of whichis hereby incorporated by reference herein in its entirety. Theanalyzers 2000, 4000 and pre-analytical system 10 are modular such thatthey can be physically connected and disconnected from one another andalso electronically connected and disconnected from one another.Although first analyzer 2000 is different from second analyzer 4000 interms of the operations and assays they perform, it should be understoodthat second analyzer 4000 can be a duplicate of first analyzer 2000 sothat pre-analytical system 10 couples to at least two of the sameanalyzers. It should also be understood that the modularity ofpre-analytical system 10 allows it to couple to any analyzer soconfigured. As shown, first and second analyzers 2000, 4000 are disposedat opposite sides of pre-analytical system 10 in a linear arrangement.Although, pre-analytical system 10 and analyzers 2000, 4000 areconfigured for this physical arrangement it is contemplated thatpre-analytical system 10 can be configured to accommodate more than twoanalyzers and that pre-analytical system 10 and analyzers 2000, 4000 canbe configured so that they can be placed in other physical arrangementssuch as in an L-shape, for example.

Analyzer in Relation to Pre-Analytic System

As depicted in FIG. 2, the first analyzer can be coupled to either sideof pre-analytical system 10. In this regard, a sample container shuttletransport assembly 300 a of pre-analytical system 10 extends toward aleft side of analyzer 2000 where analyzer 2000 is located to the rightof system 10, or a sample container shuttle transport assembly 300 b ofpre-analytical system 10 extends toward a right side of analyzer 2000where analyzer 2000 is located to the left of system 10. Such assemblies300 a-b may terminate adjacent to the analyzer's threshold as is shown.However, in some embodiments such assemblies 300 a-b may extend acrossthe analyzer's threshold and into analyzer 2000. An inventory robot2300, described further below, can retrieve a sample container shuttle2030 from such assemblies 300 a-b regardless of which side of analyzer2000 a sample container shuttle 2030 is delivered.

Structural Frame

As further shown in FIGS. 2 and 3, analyzer 2000 includes a structuralframe 2011 comprised of several support components, such as segments ofmetal tubing, which are configured to support and define various decksor levels for sample processing and analysis. Such decks may include adetection/analysis deck 2012, an inventory deck 2014, a processing deck2016, and a liquid robot handling deck 2018. However, more or less decksmay be implemented to reduce horizontal length or vertical height ofanalyzer 2000. Analyzer 2000 also includes a housing or shell 2010 thatsurrounds its internal components, as shown in FIG. 1.

Deck Relationships

Detection/analysis deck 2012 is disposed near the bottom of analyzer2000 and is located beneath inventory deck 2014. Inventory deck 2014 isdisposed between processing deck 2016 and detection/analysis deck 2012.Processing deck 2016 is disposed between inventory deck 2016 and liquidhandling robot deck 2018. Liquid handling robot deck 2018 is disposednear the top of analyzer 2000. Detection/analysis, inventory andprocessing decks 2012, 2014, 2016 are each located at the front ofanalyzer 2000 and terminate before reaching the back of analyzer so asto provide a space that spans the length of analyzer 2000 in aright-left direction and also extends along the height of analyzer 2000so as to intersect the detection/analysis, inventory, and processingdecks 2012, 2014, 2016. An inventory robot 2300 is disposed within thespace so provided that allows it to access each one of those threeaforementioned decks.

Consumables

FIGS. 4A-8 depict various consumables that can be automatically handledand utilized for performing a broad menu of assays on several categoriesof samples including blood, mucus, sputum, urine, feces, liquid basedcytological samples and the like. Such menu includes assays involvingthe detection of Chlamydia trachomatis, Neisseria gonorrhoeae,Trichomonas vaginalis, group B streptococcus, enteric bacteria (e.g.,Campylobacter, Salmonella, Shigella, Escherichia coli, Shigelladysenteriae), and enteric parasites (e.g., Giardia lamblia,Cryptosporidium, Entamoeba histolytica) and also assays involving thedetermination of blood viral loads (e.g., HIV, HCV, and HBV). Theability to perform such a broad menu of assays is partially supported bythe consumable design. Such consumables includes pipette tips, samplecontainers, sample container shuttles, processing plates, dry reagentplates, liquid reagent plates, and amplification cartridges.

Pipette Tips

Pipette tips 2020 include a first pipette tip 2020 a (FIG. 4A) and asecond pipette tip 2020 b (FIG. 4B). First pipette tip 2020 a is largerthan second pipette tip 2020 b. For example, first pipette tip 2020 amay be 1 mL tip while second pipette tip 2020 b may be a 175 uL tip.However, analyzer 2000 is capable of accommodating any size pipette tipas needed.

Sample Shuttle and Sample Container

Sample container shuttle 2030 (FIG. 5) is similar to shuttle 284 of the'349 Application and includes receptacles 2032 each configured toreceive a sample container 03. The particular shuttle 2030 depictedincludes two rows of six receptacles 2032 for a total of twelvereceptacles. However, any number of receptacles 2032 can be provided.For example, shuttle 2030 may include two rows of twelve receptacles2032 for a total number of 24 receptacles. In the particular analyzer2000 depicted, a batch of samples may include 24 total samples whichwould equate to 24 total sample containers. However, analyzer 2000 mayperform dual-lane assays, or other multiple lane assays, where a singlesample is processed and analyzed twice or more in one run. Thus, somebatches of 24 total samples may only need 12 total sample containers toget that total sample count. As such, having each shuttle 2030accommodative of half of a full sample batch provides analyzer withflexibility to efficiently accommodate dual-lane assays or othermultiple lane assays.

Shuttle 2030 also includes first transverse openings 2034 for engagementwith inventory robot 2300 and second transverse openings 2036 whichintersect corresponding receptacles 2032 to allow a sample containerretention assembly (described below) to access containers 03 disposedtherein. Sample containers 03 are the same as the third-type container03 of the '349 Application. In this regard, sample containers 03 includecaps with a penetrable seal 09.

Processing Plate

Processing plate 2040 (FIG. 6) includes a plate body 2041. Engagementmembers 2049 extend from an upper surface of plate body 2041. Suchengagement members 2049 include engagement notches 2042. Thus, notches2042 are positioned above plate body 2041 and inboard relative to sidesof plate body 2041. This allows an end effector, such as end effector2360 described further below, to grip processing plate 2040 from aboveplate body 2041. However, in some embodiments of plate 2040, notches2042 may extend into side surfaces of body 2041 which allows inventoryrobot 2300 to engage processing plate 2400 from a periphery of body2041.

Plate body 2041 at least partially defines a plurality of extractiontubes 2044, mixing wells 2046 and pipette tip holding stations 2047.Each extraction tube 2044 has a corresponding mixing well 2046 andpipette tip holding station 2047 aligned with it. Extraction tubes 2044are located closer to a midline of body 2041 than mixing wells 2046, andmixing wells 2046 are located closer to the midline of body 2041 thanpipette tip holding stations 2047. Extraction tubes 2044 have openingsdefined by body 2041 and have a tube body 2045 extending from a bottomsurface 2043 of body 2041. Tube body 2045 defines an outer surface ofrevolution, such as conical surface of revolution. Pipette tip holdingstations 2047 also have openings defined by body 2041 and a sleeve 2048that extends from bottom surface 2043. Such sleeve 2048 keeps a pipettetip 2020 stable when disposed therein even if the processing plate ismoved. Two rows of extraction tubes 2044, mixing wells 2046, and pipettetip holders 2047 are provided and are arranged parallel to each other.In the particular embodiment depicted, processing plate 2040 includestwo rows of six extraction tubes 2044, mixing wells 2046 and pipette tipholding stations 2047, which allows twelve samples to be processedtherein. However, more or less is contemplated. For example, processingplate 2040 can include two rows of twelve extraction tubes 2044, mixingwells 2046 and pipette tip holding stations 2047 or even a single row ofsuch. Processing plate 2040 includes an identifier, such as a barcode,on a side surface or other surface thereof which helps analyzer 2000identify the plate.

Dry Reagent Plates

Dry reagent plate 2050 (FIG. 7) includes a plate body 2051. Engagementnotches 2052 extend into the side surfaces 2053 of body 2051 whichallows inventory robot 2300 to engage dry reagent plate 2050 from anytwo opposing sides thereof. Plate body 2051 defines a plurality of dryreagent compartments 2054. A penetrable membrane (not shown) is placedover each of these compartments 2054 and is sealed to plate body 2051 sothat if the membrane is penetrated to obtain access to one compartment,the remaining compartments remain sealed. This allows plate 2050 to bestored until needed for another batch of samples. As depicted, there are96 total reagent compartments 2054 which allow reagent plate 2050 to beutilized for four separate runs of 24 sample batches. However, thistotal number can vary. Dry reagent plate 2050 also includes anidentifier, such as a barcode, on a side surface 2053 or other surfacethereof which helps analyzer 2000 identify the plate.

In one embodiment two dry reagent plates 2050 are utilized for eachassay: a first dry reagent plate or extraction reagent plate 2050 a anda second dry reagent plate or amplification reagent plate 2050 b (seeFIG. 10C). In this regard, extraction reagent plate 2050 a is loadedwith a lysis buffer and extraction beads, and amplification reagentplate 2050 b is loaded with a master mix reagent.

Each reagent compartment 2054 within the same plate 2050 is loaded withthe same reagent so that the reagent plate is assay specific. Thus,where more than one assay is performed by analyzer 2000, separatereagent plates each with reagents specific to that assay are utilized.Thus, for one assay performed by analyzer 2000, at least two dry-reagentplates 2050 are utilized (e.g., one extraction reagent plate 2050 a andone amplification reagent plate 2050 b). Similarly, where two differentassays are performed by analyzer 2000, at least four dry-reagent plates2050 are utilized (e.g., two extraction reagent plates 2050 a and twoamplification reagent plates 2050 b). Although, the extraction andamplification dry reagent plates 2050 a-b are described as beingseparate, it is contemplated that they may be combined into a singlereagent plate.

Liquid Reagent Plate

The liquid reagent plate 2060 (FIG. 8) includes a plate body 2061defined by upper and lower surfaces and side surfaces 2062 extendingtherebetween. Engagement notches 2064 extend into the side surfaces 2062of body 2061 which allows the inventory robot 2300 to engage liquidreagent plate 2060 from any two opposing sides thereof. Liquid reagentplate 2060 includes a plurality of reagent compartments 2066 organizedin four processing rows 2066. Each one of these rows 2066 includes fourcompartments 2066 a-d where each compartment holds a reagent for asample processing step. For example, each processing row 2066 includes afirst compartment 2066 a for a reconstitution buffer, a secondcompartment 2066 b for a wash buffer, a third compartment 2066 c for anelution buffer, and a fourth compartment 2066 d for a neutralizationbuffer. These compartments 2066 a-d are arranged in the order in whichthey are used. However, they could be in other arrangements. Inaddition, each compartment 2066 holds enough reagent to process a fullbatch of samples, for example a batch of 24 total samples. A penetrablemembrane (not shown) is placed over each of these compartments 2066 andis sealed to the plate body 2061 so that if the membrane is penetratedto obtain access to one compartment, the remaining compartments remainsealed. This allows liquid reagent plate 2060 to be stored until neededfor another batch of samples. Liquid reagent plate 2060 also includes anidentifier, such as a barcode, on a side surface 2062 or other surfacethereof which helps analyzer 2000 identify the plate.

Amplification Cartridge

The amplification cartridge 2070 (FIG. 9) is similar to the BD MAX™ PCRcartridges associated with the BD MAX™ system (Becton Dickinson,Franklin Lakes, N.J.) and is described in U.S. Pat. Nos. 7,332,130;7,998,708; 8,105,783; 8,440,149; 8,709,787; 8,765,076, the disclosuresof which is hereby incorporated herein by reference in their entirety.Amplification cartridge 2070 includes inlet ports 2073, microfluidicchannels (not shown), wax valves 2074, amplification chambers 2075, andventing holes 2076. A processed sample is inserted into cartridge 2070via inlet ports 2073 which travels down the microfluidic channels intoamplification chambers 2075. Venting holes 2076 allow air to escape asthe sample travels down the channels. Wax valves 2074, when melted, sealchambers 2075 so that amplification of the sample can occur therein.Transparent or translucent windows partially defining chambers 2075allows a detector to detect the presence of an analyte or targettherein.

Amplification cartridge 2070 also includes engagement notches 2072extending into side surfaces of cartridge 2070. These notches 2072extend into cartridge 2070 at opposite sides thereof and taper inwardlytoward a midline of the cartridge. In addition, notches 2072 are locatedat sides adjacent to the sides of the cartridge that include inlet ports2073 and vents 2076. This prevents notches 2072 from interfering withthese structures. Notches 2072 allow inventory robot 2300 to engageamplification cartridge 2070 so that cartridge 2070 can be carried byrobot 2300. Although, in some embodiments, amplification cartridge 2070may not have such notches 2072 and may employ other features forengagement with a robotic gripper. A lower surface 2079 of cartridge2070 where it intersects notch 2072 is beveled or otherwise contoured tomatch the contour of an engagement post 2365 of the robot as isdescribed further below and as illustrated in FIG. 13D, which a formsrecess or indentation 2077 in lower surface 2079 about notch 2072 thatfurther assists robot engagement. Amplification cartridge also includesan identifier, such as a barcode, on a top or bottom surface 2078, 2079thereof which helps analyzer 2000 identify the cartridge.

Consumable Staging

FIGS. 10A-10C depict various aspects of consumable staging within theinventory deck 2014 and processing deck 2016. Inventory deck 2014includes at least one consumable repository, such as consumablerepository 2110 (FIG. 10A). Inventory deck 2014 also includes at leastone waste repository, such as waste repository 2130 (FIG. 10B).Processing deck 2016 also includes a plurality of pipette tip drawerassemblies 2140 (FIG. 10C). Consumable repository 2110, waste repository2130, and pipette tip drawers 2140 are each accessible by a user fromthe front of analyzer 2000 so that the user can load and unload variousconsumables utilized by analyzer 2000.

Consumable Repository

As shown in FIG. 10A, consumable repository 2110 includes supportstructures or beams 2114 that extend horizontally from columns 2118 thatextend vertically from a base 2119. The support structures 2114 definecompartments for individual consumable items so that the consumableitems may be loaded into the compartments from a first side of thecolumns 2118 and offloaded from a second side of the columns 2118. Forexample, support structures 2114 may slidingly receive and support a dryreagent plate 2050 or a liquid reagent plate 2060 as shown in FIG. 10A.Such plates 2050 and 2060 may be slid into their respective compartmentsfrom a front side of columns 2118 by a user so that an identifier, suchas a bar code, is facing toward an interior of system 2000. An inventoryrobot 2300, described further below, may scan the identifier to identifythe particular plate and remove the appropriate plate 2050, 2060 from aback side of columns 2118 as needed. In this regard, consumable items,such as plates 2050 and 2060, may be loaded by a user in any order assystem 2000, with assistance from robot 2300, can conduct an inventoryand automatically determine the order in which the consumables wereloaded by the user. In addition, support structures 2114 hold plates2050, 2060 at a lower end thereof so that openings 2052, 2064 thereofare exposed thereby allowing robot 2300 to engage a selected plate forremoval from their respective compartments. Also as shown, amplificationcartridges 2070 may be stacked within respective cartridge storagecompartments 2116 at a top end of consumable repository 2110. Cartridges2070 can be stacked by a user in storage compartment 2116 from the frontside of system 2000 and removed therefrom by robot 2300.

In one embodiment, consumable repository 2110 may be attached to a setof tracks that allows repository 2110 to be pulled out like a drawer forrestocking. A pneumatic piston (not shown) may assist in openingrepository 2110 and may also provide damping to prevent repository 2110from closing too quickly and jostling the consumables out of position.In other embodiment, repository 2110 can be hinged so that door 2112 canswing open toward the user revealing the repository for restocking.

Waste Repository

Waste repository 2130 (FIG. 10B) includes a door 2132 that is accessedby the user at the front of analyzer 2000. A waste compartment 2134,which has an opening 2136 parallel to door 2132, is attached to abackside of door 2132. Repository 2130 also includes a shelf 2138extending from waste compartment 2134. This shelf 2138 allows usedprocessing plates 2040 to be stacked by inventory robot 2300 thereon asdepicted. Repository 2130 may also contain a liquid container withinopening 2136 that may communicate with one or more liquid wastereceptacles 2260 (see FIG. 11B) located on processing deck 2016. Wasterepository 2130 may be attached to a set of tracks that allowsrepository 2130 to be pulled out like a drawer for emptying. A pneumaticpiston (not shown) may assist in opening repository 2130 and may alsoprovide damping to prevent repository 2130 from opening too quickly andjostling processing plates 2040. Alternatively, repository 2130 can behinged so as to swing open toward the user for emptying.

Pipette Tip Drawers

Pipette tip drawer assembly 2140 (FIG. 10C) includes a tip drawer 2142that is generally a box-like structure that includes sidewalls 2144 andtransverse walls 2145 that includes one or more openings for receipt ofa pipette tip rack carrying a plurality of pipette tips. In theembodiment depicted, there are two openings in transverse wall 2145 oftip drawer 2142 for receipt of two pipette tip racks (not shown). Afirst rack may include first pipette tips and a second rack may includesecond pipette tips. Pipette tip drawer 2142 is attached to one or moretracks 2148 that allows drawer 2142 to be partially pulled out ofanalyzer 2000 for removal of empty tip racks and restocking with freshtip racks. A door (not shown) may be attached to one end of drawer 2142so that when drawer 2142 is closed, the door forms a portion of theanalyzer's outer shell. A pneumatic piston 2149 may assist in openingdrawer 2142 and may also provide damping to prevent drawer 2142 fromopening or closing too quickly.

Processing Modules

Processing Modules/Lanes

FIG. 11A depicts processing deck 2016 which includes a plurality ofprocessing modules 2200 arranged side-by-side. As shown, processing deck2016 includes three processing modules: a first processing module 2200a, as second processing module 2200 b, and a third processing module2200 c. However, analyzer 2000 can include more or less processingmodules 2200 to accommodate the throughput needs and space requirementsof a particular laboratory. Processing modules 2200 a-c are similarlyconfigured in terms of their physical arrangement with the differenceamong them being their location relative to a shuttle platform having ajaw assembly that functions as a sample container retention assembly2210 which may be shared by adjacent modules. For example, first andsecond processing modules 2200 a-b may both utilize a first samplecontainer retention assembly 2210 ab to retain sample containers 03therefor, and second and third processing modules 2200 b-c may bothutilize a second sample container retention assembly 2210 bc to retainsample containers 03 therefor.

Although each processing module 2200 is similarly configured, eachprocessing module 2200 is capable of performing a wide array of assaysso that each processing module 2200 can run an assay that is differentfrom an assay being performed concurrently in another processing module.In this regard, each processing module 2200 can be automaticallydesignated and redesignated to perform any number of assays typesdepending on the processing needs at a particular point in time. Forexample, first processing module 2200 a may be designated to perform afirst assay, second processing module 2200 b a second assay, and thirdprocessing module 2200 c a third assay where each assay is different.However, when those assays are completed, any one of the processingmodules 2200 a-c can be automatically redesignated to perform adifferent assay, so that each of the first, second, and third processingmodules 2200 a-c run the same assay, for example. As such, the analyzer2200 is flexible to accommodate real-time needs provided sufficientconsumables for a particular assay are inventoried within its housing2010.

Example of Processing Module

FIG. 11B depicts first processing module 2200 a and is exemplary of theother processing modules. First processing module 2200 a generallyincludes the first sample container retention assembly 2210 ab (which isshared by second processing module 2200 b), a dry-reagent station 2220,a liquid reagent station 2230, extractors 2240, an amplificationcartridge station 2250, pipette drawers 2140, and a waste receptacle2260. These components can be arranged in any configuration. However, inthe embodiment depicted, dry-reagent station 2220 and liquid reagentstation 2230 are located at a backend of processing deck 2016 anddisposed adjacent to each other. A first and second extractor 2240 a-bare located adjacent reagent stations 2220 and 2230 and are positionedbetween amplification cartridge station 2250 and reagent stations 2220,2230. This allows for the efficient transfer of liquid therebetween.Pipette tip drawers 2140 are located at the front of processing deck2016 allowing a user to have easy access thereto. Processing module 2200a preferably includes three pipette tip drawers 2140 each holding afirst pipette tip rack 2022 a carrying first pipette tips 2020 a and asecond pipette tip rack 2022 b carrying second pipette tips 2020 b. Thisamount of pipette tips 2020 allows processing module 2200 a to performabout twelve assay runs without restocking. Sample container retentionassembly 2210 ab is disposed to the side of extractors 2240 a-b andreagent plate stations 2220, 2230 and between first and secondprocessing modules 2200 a-b. Also between first and second processingmodules 2200 a-b is a waste receptacle 2260. Waste receptacle allowsused pipette tips to be discarded into waste repository 2130 from aboveprocessing deck 2016. Waste receptacle 2260 may also include a liquidwaste inlet (not shown) that allows liquid waste to be disposed into abottle or some other container within the waste repository 2130.

Sample Container Retention Assembly

Sample container retention assembly 2210 ab is similar to samplecontainer retention assembly 1100 of the '349 Application in that itincludes a clamping assembly 2212 that closes toward a shuttle 2030disposed within the clamping assembly to retain shuttle 2030 andcontainers 03 within the shuttle 2030 while aliquots are aspirated fromcontainers 03. In this regard, clamping assembly 2212 includesengagement members 2214 which are configured to project through secondtransverse openings 2036 in shuttle 2030 when clamping assembly 2212 isclosed to engage a skirt 07 at a bottom end of sample containers 03, asbest seen in FIG. 11C. These engagement members 2214 penetrate/bite intoskirts 07 of respective containers 03 to prevent containers 03 frombeing inadvertently removed from shuttle 2030 during aspiration.However, unlike retention assembly 1100, retention assembly 2210 ab hasa stationary platform 2216 upon which shuttle 2030 rests, whereasretention assembly 1100 utilizes a moving conveyor 1116. Thus, insteadof a conveyor to transport a shuttle 2030 into position within clampingassembly 2210 ab, inventory robot 2300 places shuttle 2030 into positionwithin clamping assembly 2212.

Reagent Plate Stations

Dry reagent plate station 2220 and liquid reagent plate station 2230 mayeach include a receptacle defined by a support structure (not shown),such as a pair of rails, extending from a surface of deck 2016. Suchreceptacles may receive a corresponding reagent plate to help ensureeach plate is placed in a precise location. As shown, processing module2200 a includes one dry reagent plate station 2220 and one liquidreagent plate station 2230. Since analyzer 2000 typically utilizes twodry reagent plates 2050 a-b for each assay performed, dry reagent plates2050 a-b are exchanged during operation. However, it is contemplatedthat an additional dry reagent plate station may be incorporated intoprocessing module 2200 a to allow each of reagent plates 2050 a-b to belocated on processing deck 2016 at one time. Processing module 2200 amay also include a recessed support structure that allows anamplification cartridge 2070 to be precisely placed by inventory robot2300.

Extractor

An extractor assembly, as depicted in FIGS. 12A and 12B, includes twoextractors: a first extractor 2240 a and a second extractor 2240 b. Eachextractor 2240 a-b includes a housing 2242, printed circuit boards 2247(“PCB”), a motor 2244, a drive mechanism 2246, permanent magnets 2241and heating elements 2248. Other exemplary extractor assemblies includethe extractor of the BD MAX™ system (Becton Dickinson, Franklin Lakes,N.J.) and is described in U.S. Pat. No. 8,133,671, the disclosure ofwhich is hereby incorporated herein by reference in its entirety.Permanent magnets 2241 are mounted to drive mechanism 2246 and aredisposed within housing 2242. Permanent magnets 2241 are arranged in tworows of six magnets so as to form six pairs of adjacent magnets 2241a-b. This side-by-side pairing of magnets 2241 a-b has been found toenhance the magnetic attraction of magnetic beads within a processingplate 2040 over that of a single magnet. The rows of magnets 2241 aremoveably connected to drive mechanism 2246 and are moveable into and outof housing 2242 through an opening at the top of housing 2242 via drivemechanism 2246 which is operated by motor 2244.

PCBs 2247 and heating elements 2248 are connected to opposing sides ofhousing 2242. Heating elements 2248 are arranged in two rows of six andextend above housing 2242. Each heating element 2242 defines a recess2249 that forms a cup-like structure that has a geometry conforming tothe outer surface of revolution of a processing plate's extraction tube2045. This allows heating elements 2248 to directly contact such surfaceof revolution to transfer heat into extraction tubes 2045 and alsoallows processing plates 2040 to be supported by an extractor 2240 in astable manner. In addition, the width of extractors 2240 a-b are suchthat when a processing plate is retained thereby, pipette tips 2020 canbe placed into pipette tip holding stations and extend throughprocessing plate 2040 without any interference by extractor 2240. Whenmotor 2244 is operated, the rows of permanent magnets 2241 may be movedup into a space 2243 between heating elements 2248 and adjacentextraction wells 2045 to attract magnetic beads that may be disposedtherein.

FIGS. 12C and 12D depict an extractor 2240′ and processing plate 2040according to further embodiments of the present disclosure. Aspreviously described, processing plate can include engagement notches2042 in opposing sides of plate body 2041. However, instead ofengagement notches 2042 being located on sides of plate body 2041,processing plate 2040 preferably includes engagement members 2049 whichextend from an upper surface of plate body 2041. Such engagement members2049 include engagement notches 2042. Thus, processing plate 2040locates notches 2042 above plate body 2041 and inboard relative to thesides of plate body 2041. This allows end effector 2360 to gripprocessing plate 2040 from above plate body 2041 rather than at sidesthereof which allows end-effector 2360 to operate in spaces with littleclearance, as is described in more detail below.

Extractor 2240′ is similar to extractor 2240 with the difference beingthat extractor 2240′ includes a drip tray 2280. Drip tray 2280, asshown, includes trough members 2281 a-b connected by an intermediatemember 2088. Intermediate member 2088 extends between opposing sides ofextractor 2240′ and includes an opening for extraction tubes 2045 andmixing wells 2046 to extend therethrough so that extraction tubes 2045can engage heating elements 2248 of extractor 2240′, as best shown inFIG. 12D. In addition, intermediate member 2088 helps support processingplate 2040 as it generally has a flat upper surface which allowsprocessing plate body 2041 to rest thereon. Each trough member 2281 a-bincludes an outer shield 2082, inner shield 2084, and lower shield 2086.Inner shield 2084 is connected to intermediate member 2088 and extendsdownwardly therefrom so that, when the processing plate 2040 is mountedto extractor 2240′, inner shield 2084 is located between the heatingelements 2248 and a row of pipette sleeves 2048, as best shown in FIG.12D. Lower shield 2086 connects to and extends between the outer andinner shields 2082, 2084. Outer shield 2082 extends upwardly from lowershield 2082. This configuration forms a trough that is sized to receivea row of pipette tips 2020 when such pipette tips 2020 are disposed inrespective ones of pipette sleeves 2048. In this regard, trough members2281 a-b form a barrier within system 2000 that helps preventcontamination from pipette tips 2020 which may be stored in pipettesleeves 2048 for reuse.

FIG. 12E depicts third processing module 2210 c which includesextractors 2240′. Processing plates 2040 are mounted to said extractors2240′. Extractors 2240′ and processing plates 2040 are disposed betweendry and liquid reagent plates 2050, 2060 and a pipette tip chute 2135and amplification card station 2070. However, as shown, processingplates 2040 generally sit lower on processing deck 2016 than thesesurrounding components. However, to help conserve the overall size ofsystem 2000, the side-to-side clearance between these components andprocessing plates 2040 is minimal. Thus, it may be difficult for endeffector 2360 to have enough clearance to place processing plates 2040onto and pick-up processing plates 2040 from extractors 2240′. In thisregard, processing plates 2040 provide engagement members 2049 whichprovide sufficient clearance for end effector 2360 to pick and placeprocessing plate 2040. Also, as shown, elongate openings 2017 extendthrough processing deck surface 2016 which allows reusable pipette tips2020 mounted to processing plate 2040 to extend therethrough. Troughmembers 2281 a-b of drip tray are aligned with such openings 2017 whichshield system 2000 from being contaminated by drippings from suchpipette tips 2020.

Detector

Each processing module 2200 a-c has an associated detector 2270, whichin the embodiment depicted in FIG. 10A, are each located indetection/analysis deck 2012 at the bottom of analyzer 2000. Forexample, first processing module 2200 a is associated with a firstdetector 2270 a, second processing module 2200 b is associated with asecond detector 2270 b, and third processing module 2200 c is associatedwith a third detector 2270 c. The location of detectors 2270 a-c beneathprocessing deck 2016 helps isolate detectors 2270 a-c from possiblecontaminants An exemplary detector is the detector of the BD MAX™ system(Becton Dickinson, Franklin Lakes, N.J.) and is described in U.S. Pat.No. 8,133,671, the disclosure of which is hereby incorporated herein byreference in its entirety. Each of the detectors 2270 a-c includes areader head 2271 and a thermocycler 2275. Reader head 2271 includes anoptical emitter and a detector (not shown) that is configured detect thepresence of fluorescent probes within a chamber 2075 of amplificationcartridge 2070. Thermocycler 2275 includes a moveable platform 2276 thathas a recess 2277 configured to receive an amplification cartridge 2070.Thermocycler 2275 has heating elements (not shown) that periodicallyheat the contents of amplification cartridge 2070, such as purified DNA,to predetermined temperatures to assist in the amplification of suchcontents. Reader head 2271 is suspended from the structure of analyzer2000 such that the reader thereof points in a downward direction.Thermocycler 2275 is disposed beneath reader head 2271 and includes amotor 2278 and drive screw that moves platform 2276 in a verticaldirection to press an amplification cartridge 2070 against reader head2271. The space that exists between thermocycler 2275 and reader head2271 is sufficiently wide to allow inventory robot 2300 to placeamplification cartridge 2070 onto thermocycler 2275.

Consumable Handling

FIGS. 13A-13D depict the inventory robot 2300 according to oneembodiment of the present disclosure. Inventory robot 2300 helpsinventory all consumables within analyzer 2000 and also handles allconsumables within analyzer 2000. In addition, inventory robot 2300 canreach out of analyzer 2000 into pre-analytical system 10 so as to move ashuttle 2030 with sample containers 03 back and forth between analyzer2000 and pre-analytical system 10. In this regard, housing of analyzer2000 may include a side opening at the left or right sides thereof thatare sized to allow robot 2300 to reach therethrough. Inventory robot2300 includes a track member 2310, a body/post 2320, a shoulder 2330, afirst arm member 2340, a second arm member 2350, and an end effector orhand 2360.

Robot Arm

Track member 2310 extends from one side of analyzer 2000 to the other ina right-left direction and is located nearer the backend of analyzer2000 than the aforementioned front located decks 2012, 2014, and 2016.Body 2320 is slidably attached to track member 2310 and orthogonallyextends therefrom. Body 2320 is coupled to track member 2310 via acarriage 2322. Carriage 2322 and track member 2310 form a linear motorthat allows body 2320 to be translated along a single axis in theleft-right direction. An example of a linear motor that can beimplemented in analyzer 2000 is the Festo Linear Motor Actuator (“FLMA”)(Festo AG & Co. KG Esslingen am Neckar, Germany). However, other drivemechanisms, such as a belt and pulley mechanism are contemplated todrive body 2320 along track member 2310.

Shoulder 2330 is slidably attached to body 2320 so that shoulder 2330can be driven along a vertical axis of body 2320 which may also beachieved by a linear motor or some other drive mechanism. Shoulder 2330is attached to first arm member 2340 at one end of first arm member 2340so that the first arm member 2340 is rotatable about a vertical axisshared by both shoulder 2330 and first arm member 2340. Second armmember 2350 is connected to the other end of first arm member 2340 sothat second arm member 2350 can rotate about a vertical axis shared byboth arm members 2340 and 2350. End effector 2360 is connected to an endof second arm member 2350 remote from first arm member 2340 and isrotatable about a vertical axis shared by end effector 2360 and secondarm member 2350.

End Effector

End effector 2360 includes a body 2362 and a pair of moveable fingers2363 a-b coupled to body 2362. Moveable fingers 2363 a-b are operable sothat they move closer together or farther apart in order to grasp orrelease an item, as is illustrated in FIG. 13A. In this regard, moveablefingers 2363 a-b generally remain parallel during operation. Body 2360includes one or more identifier reader 2366, such as a barcode scanner,in a surface of body 2362 that generally faces a direction away fromfingers 2363 a-b. Body 2362 is capable of rotating about 180 degreesrelative to second arm member 2350 which allows such identifier reader2366 to face toward the front of analyzer 2000 and scan consumableslocated in inventory deck 2014 or elsewhere. Body 2362 may also includea identifier reader in a bottom surface thereof so that such reader canread upward facing identifiers, such as those that may be located onamplification cartridge 2070.

Fingers 2363 a-b are particularly configured to engage various differentconsumables. In this regard, fingers 2363 a-b include first engagementfeatures 2361 and second engagement features 2364. First engagementfeatures 2361, as shown, are tabs or projections that extend inboardfrom one finger 2363 toward the other finger 2363. First engagementfeatures 2361 are sized to fit within engagement notches 2042, 2052,2062 of plates 2040, 2050, 2060, respectively, and first transverseopenings 2034 of shuttle 2030. In operation, as fingers 2363 a-b areclosed onto a consumable item, first engagement features 2361 extendinto the notches or openings of the corresponding consumable itempreventing the consumable item from falling while fingers 2363 a-bthemselves clamp to side surfaces of the consumable item to furthercontrol and retain such item. As shown, each finger 2363 a-b preferablyincludes two engagement features 2361 which helps prevent inadvertentrotation of the consumable item within the fingers' grasp.

Second engagement features 2364 are generally located at opposite sidesof fingers 2363 a-b than first engagement features 2361 and include adownwardly extending post or dovetail 2365. Post 2365 extends from agenerally planar bottom surface 2366 of engagement feature 2364 andtapers outwardly therefrom to form a frustoconical surface ofrevolution, as best shown in FIG. 13C. These posts 2365 engage acorresponding notch 2072 in an amplification cartridge 2070. Asdiscussed above, amplification cartridge 2070 includes a beveled orcontoured surface about each notch 2072 which forms an indentation 2077.In operation, as posts 20365 slide into a respective notch 2072, thepost 2365 eventually reaches this indentation 2077. When it reachesindentation 2077, post 2365 is received within indentation 2077 in aconforming manner, as is illustrated in FIG. 13D. This helps provide astable platform for cartridge 2070 to be moved around analyzer 2000 asindention 2077 conforms to the post's surface of revolution. Inaddition, the flare or taper of post 2365 helps prevent cartridge 2070from falling.

As shown in FIG. 13B, each finger 2363 a-b includes three engagementfeatures 2364. However, while more or less engagement features 2364 arecontemplated, it is preferable that each finger 2363 a-b include asingle second engagement feature 2364. This allows fingers 2363 tosufficiently engage an amplification cartridge 2070 that may beinadvertently rotated about a vertical axis so that its sides are notparallel with fingers 2363 a. This may be a significantly more difficulttask for fingers 2363 a-b with more than a single engagement feature2364 as at least some of features 2364 may not be able to properly alignwith corresponding notches 2072 of amplification cartridge 2070 in theevent such cartridge 2070 is inadvertently rotated.

Also each finger 2363 a-b may be flexible so as to be able to benddownwardly or upwardly about a horizontal axis while being resilientenough so as to not yield too readily to contact.

Such flexibility can be imparted on each finger 2363 a-b along a lengthnear a terminal end thereof that includes second engagement feature2364. This allows fingers 2363 a-b to automatically adjust to engage anamplification cartridge 2070 that may be tilted about a horizontal axisso that cartridge 2070 is not parallel to fingers 2363 a-b.

Liquid Handling

FIGS. 14A and 14B depict a liquid handling robot 2400 according to oneembodiment of the present disclosure. Liquid handling robot 2400 issuspended at liquid handling robot deck 2018 and above processing deck2016. Liquid handling robot 2400 includes a track member 2405 thatextends from one side of analyzer 2000 to another in a right-leftdirection. A plurality of multichannel pipettors 2440 is connected totrack member 2405 via carriages 2420 and transverse arms 2430. Arms 2430are connected to carriages 2420 and carriages 2420 are slidablyconnected to track member 2405 so that arms 2430 extend in a directiontransverse relative to the track member 2405. Carriages 2420 and trackmember 2405 form a linear motor that allows multichannel pipettors 2440and arms 2430 to be driven along track member 2405 in the left-rightdirection. An example of such a linear motor is the Festo Linear MotorActuator (“FLMA”) (Festo AG & Co. KG Esslingen am Neckar, Germany). Asshown, there is one multichannel pipettor 2440 for every processingmodule 2200. Thus, in this particular embodiment, there are threepipette assemblies: a first multichannel pipettor 2440 a, a secondmultichannel pipettor 2440 b, and a third multichannel pipettor 2440 b.First multichannel pipettor 2440 a corresponds to first processingmodule 2200 a, second multichannel pipettor 2440 b corresponds to secondprocessing module 2200 b, and third multichannel pipettor 2440 ccorresponds to third processing module 2200 c. However, more or lessmultichannel pipettors 2440 are possible and are based on the number ofprocessing modules 2200.

Multichannel Pipettor

FIG. 14B depicts multichannel pipettor 2442 according to an embodimentof the present disclosure which is exemplary of multichannel pipettors2440 a-c. Multichannel pipettor 2442 includes a backplane connector 2450and a plurality of liquid handling assemblies 2442 connected tobackplane connector 2450. In the embodiment depicted, there are threeliquid handling assemblies 2442: a first liquid handling assembly 2442a, a second liquid handling assembly 2442 b, and third liquid handlingassembly 2442 c. However, more or less is contemplated. Each liquidhandling assembly 2442 includes a main board assembly 2460 and a pipetteassembly 2470. Liquid handling assemblies 2442 a-c are connected tobackplane connector 2450 adjacent to one another in close proximity.

Each main board assembly 2460 helps provide data, power andpositive/negative air pressure to a corresponding pipette assembly 2470.In the embodiment depicted, there are three pipette assemblies 2460: afirst pipette assembly 2460 a, second pipette assembly 2460 b, and athird pipette assembly 2460 c. These assemblies 2460 a-c correspond to arespective liquid handling assembly 2442 a-c. Each main board assembly2460 is similar to the main board assembly 1401 described and shown inFIGS. 27A and 27B of the '349 Application. In this regard, each mainboard assembly 2460 includes a housing 2462 with various componentsdisposed therein, such as a PCB, positive and negative pressure inputs,a valve, and a liquid/gas conduit in communication with the inputs andvalve. Main boar assemblies 2460 a-c also includes a z-drive mechanismthat includes a vertical rail 2464 on one side of housing 2462 and amotor 2466 and drive shaft (not shown). The drive shaft is disposedwithin housing 2462.

Each pipette assembly 2470 is similar to the pipette assembly 502 ofFIGS. 17A-17D and pipette assembly 1402 of FIGS. 27A and 27B of the '349Application with the exception that each pipette assemblies 2470 is nothingedly connected to its respective main board assembly 2460 and doesnot rotate into multiple hinge positions. Each pipette assembly 2470 isconstrained from rotation and moves in a vertical z-direction alongvertical rail 2464 via motor 2466. Thus, the first, second, and thirdpipette assemblies 2470 a-c are capable of moving independently in avertical or z-direction. Otherwise pipette assembly 2470 is constructedsimilarly to pipette assemblies 502 and 1402 particularly with regard toits pipette channel assembly (not shown) and pipette tip ejectorassembly 2472.

Backplane connector 2450 is similar to the backplane connector 1600 ofFIGS. 29A and 29B of the '249 Application with the exception thatbackplane connector 2450 is configured to have multiple liquid handlingassemblies 2442 mounted thereto, such as the first, second, and thirdassemblies 2442 a-c illustrated. In this regard, backplane connector2450 connects to main board assemblies 2470 a-c of each liquid handlingassembly 2442 and includes several connectors (not shown), such asEthernet, multipin, positive pressure input, and negative pressure inputconnectors for supplying the liquid handling assemblies 2442 a-c withthe requisite power, pressure, and data signals. This helps reduce oreliminate external cabling that could snag and can be difficult tomanage with multiple liquid handling assemblies 2442 being connected insuch close proximity.

Automation

FIG. 15 depicts a general architecture of a computing system of analyzer2000. Computing system 2510 may be a subsystem within system 1300 ofFIG. 26 of the '249 Application which depicts a computing system diagramof the high-throughput system 00. In this regard, cross instrument bus2504 and work flow computing device 2540 are the same as bus 1320 andcomputing device 1330 depicted in FIG. 26 of the '249 Application. Inaddition, computing device 2510 is similar to computing device 1360 andis described in more detail herein along with its inputs and outputswithin analyzer 2000.

Computer control device 2510 may be any general purpose computer and maycontain a processor 2512, memory 2514 and other components typicallypresent in general purpose computer control devices. Although computercontrol device 2510 can include specialized hardware components toperform specific computing processes. Processor 2512 may be anyconventional processor, such as a commercially available CPU.Alternatively, processor 2512 may be a dedicated component such as anapplication specific integrated circuit (“ASIC”) or other hardware-basedprocessor.

Memory 2514 may store information accessible by processor 2512,including instructions 2516 that can be executed by processor 2512.Memory 2514 can also include data 2518 that can be retrieved,manipulated or stored by processor 2512. Memory 2514 can be of anynon-transitory type capable of storing information accessible byprocessor 2512, such as a hard-drive, memory card, ROM, RAM, DVD,CD-ROM, write-capable, and read-only memories.

Instructions 2516 can be any set of instructions to be executeddirectly, such as machine code, or indirectly, such as scripts, byprocessor 2512. In that regard, the terms “instructions,” “application,”“steps,” and “programs” can be used interchangeably herein. Instructions2516 can be stored in object code format for direct processing byprocessor 2512, or in any other computing device language includingscripts or collections of independent source code modules that areinterpreted on demand or compiled in advance.

In one embodiment of analyzer 2000, computing system 2510 may includeseveral sets of instructions. For example, each assay to be performedmay have several sets of instructions associated with it which mayinclude instructions that operate inventory robot 2300 to perform aninventory check and to retrieve the appropriate reagents and otherconsumables for that assay. In another example, a set of instructionsmay determine the sequence of operations performed by a particularmultichannel pipettor 2440 to assist in processing a sample foranalysis.

Data 2518 can be entered and viewed through a graphical user interface(“GUI”) which may be displayed on display interface 2500 which isspecifically associated with analyzer 2000, or display interface 1332 ofFIG. 1 and FIG. 26 of the '349 Application which is associated with theentire high-throughput system 00. Data 2518 can also be entered fromscanners, such as scanner 2366 on end effector 2360 of inventory robot2300 or scanners within pre-analytical system 10. Data can also beobtained by sensors, such as optical sensors, temperature sensors andthe like, to obtain information regarding certain conditions andactivities occurring within analyzer, such as the location of particularconsumables and air quality, for example.

This data 2518 can be digitally tagged to particular identificationcodes (e.g., barcode serial numbers) in a field implemented orrelational database, which may also be stored in memory 2514. This helpsanalyzer 2000 keep track of various consumables within analyzer 3000 andhelps provide certain information to processor 2512 during the executionof processor instructions 2516 without the need for user input. Forexample, a liquid reagent plate 2060 may have an identification codewhich may be associated with a bar code located on an outer surfacethereof which may be tagged in the database with certain stored datasuch as the type of reagents stored therein and which reagents havealready been utilized. This allows analyzer to check its inventory todetermine when reagents and other consumables are running low or areinsufficient to perform additional assays. In another example, a shuttle2030 may have an identification code which may be tagged in the databasewith certain stored data such as data involving each of the samplecontainers 03 carried by shuttle 2030 such as patient name, assay to beperformed, processing parameters and the like. In a further example,when analysis is completed, the result of the assay can be associatedwith the particular sample within the database so that a user can easilyretrieve the results via access to the workflow computing device 2540 assuch results may be communicated thereto by device 2510.

Although FIG. 20 functionally illustrates processor 2512, memory 2514,and other elements of computer control device 2510 as being within thesame block, computer control device 2510, processor 2512, and/or memory2514 can be comprised of multiple processors, computer control devices,and memories, respectively, which may or may not be stored within thesame physical housing. For example, memory 2514 can be a hard drive orother storage media located in housings different from that of computercontrol devices 2510. Accordingly, references to processor 2512,computer control device 2510, and memory 2514 should be understood toinclude references to a collection of processors, computer controldevices, and memories that may or may not operate in parallel.

Display Interface

Display interface 2520 may be associated specifically with analyzer 2000and may only display information regarding analyzer 2000 and may also beintegrated into the structure of analyzer 2000. However, displayinterface 2520 is optional (indicated by dashed lines in FIG. 15) and,in the embodiment depicted in FIG. 1, is not included as the overallsystem display interface 1332 is utilized instead. However, wheredisplay interface 2520 is included, interface 2520 may be a monitor, LCDpanel, or the like coupled to a front panel of housing 2010 or locatedremote from analyzer 2000. Display interface can display a GUI, userprompts, user instructions and other information that may be relevant toa user.

Input Interface

User control/input interface 2530 allows a user to navigate the GUI, andagain, may be optionally provided as a separate component from theoverall system input interface which is provided by display interface1332 of FIG. 1. However, where user control/input interface 2530 isprovided, such interface can be a touch panel, keyboard, or mouse, forexample. In addition, input interface 2530 can be integrated intodisplay interface 2520 such that the same device that displays promptsand the like is the same device that allows a user to respond to saidprompts.

As depicted in FIG. 15, computer control device 2510 may be connected toworkflow computing device 2540 which is utilized to integrate all of thecomponents of high-throughput system 00 such as the second analyzer 4000and pre-analytical system 10 and to integrate with a particularlylaboratory's laboratory information system (“LIS”). Thus informationrelevant to analyzer 2000 originating within pre-analytical system 10can be communicated to analyzer 2000 via workflow computing device 2540.Similarly, information relevant to pre-analytical system 10 thatoriginates from analyzer 2000 may be communicated via computer controldevice 2500 to workflow computing device 2540 which communicates thatinformation to pre-analytical system 10. Such information can also besupplemented with information obtained from the LIS by workflowcomputing device 2540, such as patient information and the like.

Computer control device is also connected to multiple components withinanalyzer 3000 to share information back and forth such as instructionsand data. Some of the components that are connected with computercontrol device via internal bus includes each of the processing modules2200 a-c, inventory robot 2300, detectors 2270 a-c, and liquid handlingrobot 2400. Such connections with computer control device 2510 allowscomputer control device 2510 to provide instructions to such componentsand receive information therefrom. For example, inventory robot 2300 mayreceive instructions from computer control device 2510 to retrievecertain consumables and place them at a particular location and maycommunicate inventory information to computer control device 2510. Thusoperations performed by the internal components of analyzer 2000 aregenerally as a result of instructions provided by processor 2512 asanalyzer 2000 is fully automated.

Method

Step 1: Receive Order

In a method of operation of analyzer 2000 (FIG. 16), an order for anassay may be received 2602 by analyzer 2000 from workflow computingdevice 2540. Such order may be first communicated from pre-analyticalsystem 10 to workflow computing device 2540 when a batch of samples ispreprocessed thereby and ready to be analyzed. In this regard,pre-analytical system 10 may load shuttles 2030 with a complete batch,which in this embodiment includes two shuttles 2030 of twelve samplecontainers 03 per shuttle 2030. Such shuttles 2030 are parked at adocking station 260 of FIG. 12A of the '349 Application.

Step 2: Inventory

Once the order is received by analyzer 2000, inventory robot 2300inventories 2604 the consumables to determine if there is a sufficientamount of consumables to perform the ordered assay. Such inventory maybe performed by inventory robot 2300. In this regard, when an order isreceived, inventory robot 2300 moves end effector 2360 toward inventorydeck 2014 beneath processing deck 2016. End effector 2360 is rotatedabout 180 degrees so that identifier reader 2366 faces toward inventorydeck 2014. Inventory robot 2300 then proceeds to scan the consumableslocated therein to determine which consumables are loaded withinanalyzer 2000. Analyzer 2000 then determines whether or not there aresufficient consumables to perform the ordered assay. Other automatedapparatus for monitoring consumable inventory are contemplated. Suchother automated methods for tracking the consumable inventory are wellknown to those skilled in the art and not discussed in detail herein.

Inventory robot 2300 may not need to scan consumables every time anorder is received. Instead, analyzer 2000 keeps track of consumablesinput into analyzer 2000 via a user. For example, when a user loads theconsumables, inventory robot 2300 scans the consumables and logs theminto a database within memory 2514. Analyzer 2000 keeps track of whenconsumables are used. Thus, analyzer 2000 can inventory the consumablesin response to an order by scanning, via processor 2512, a databasewithin its memory 2514 to determine which consumables have been used andnot used to obtain a complete tally.

In one example, an assay order to identify the presence of a particularassay target, such as Chlamydia, for example, is received by analyzer2000. Analyzer 2000 knows which reagents must be present within analyzer2000 to perform the assay. In addition, analyzer 2000 knows what otherconsumables must be used, such as pipette tips 2020, a processing plate2040 and amplification cartridge 2070. Such information may bepreprogramed in its memory 2514. Analyzer 2000 scans a database in itsmemory 2514 or utilizes inventory robot 2300 to verify that therequisite consumables are available for use.

If the consumables available are insufficient to perform the orderedassay, a user is notified 2620, which may be in the form of an alertdisplayed on display 1332 or 2520, a push notification to a mobiledevice, or an email. If other samples that require a different assay areready for processing by analyzer 2000 and there are sufficientconsumables to perform the assay, analyzer 2000 may accept thosecontainers 03 instead so as to avoid downtime until user loads analyzer2000 with the requisite consumables.

When the user does load the consumables and such consumables arereceived 2622 by analyzer 2000, such as at the beginning of a work shiftor in response to an alert that there are insufficient consumables, userloads the consumables through the front of analyzer 2000. Thus, user mayload pipette tips 2020 into pipette drawers 2142, reagent plates 2050and 2060, amplification cartridges 2070 and/or processing plates 2040into consumable repository 2110. Enough consumables can be loaded toallow analyzer 2000 to run continuously for 24 hours straight.

When such consumables are loaded by the user, analyzer 2000 recognizesthat inventory deck 2014 had been accessed, such as via door sensors.Inventory robot 2300 may then automatically perform an inventory scan toidentify any new consumables loaded into the analyzer 2000. Identifierslocated on the consumables, such as the reagent plates 2050, 2060,processing plates 2040, tip racks 2022, and amplification cartridges2070, are used to determine what the consumable are and what theycontain, such as reagents in the case of the reagent plates 2050 and2060.

Step 3: Retrieve Sample Container

Once analyzer 2000 determines there are sufficient consumables toperform the assay and that one of the processing modules 2200 isavailable for use, analyzer 2000 communicates its readiness to workflowcomputing device 2540. Workflow computing device 2540 then notifiespre-analytical system 10 which, in response, loads a shuttle 2030containing sample containers 03 onto a shuttle transport assembly 300and sends it toward analyzer 2000. Shuttle 2030 may stop just before itreaches the threshold of analyzer 2000. Although in some embodimentsshuttle 2030 may be conveyed directly into analyzer 2000.

Inventory robot 2300 then moves toward pre-analytical system 10 andreaches 2606 into pre-analytical system 10. End effector 2360 gripsshuttle 2030 so that first engagement features 2361 are received insecond transverse openings 2036. Shuttle 2030 is then transported intoanalyzer 2000 and to a shuttle retention assembly 2210 adjacent thedesignated processing module 2200 and places shuttle 2030 down ontostationary platform 2216. Clamping assembly 2212 then closes so thatengagement members 2214 extend through second transverse openings 2034and penetrate into skirts 07 of respective containers 03 therebyretaining containers 03 in position for aspiration by a multichannelpipettor 2440.

Step 4: Stage Consumables and Aliquot

With sample containers 03 sufficiently retained, processing module 2200is staged with appropriate consumables. In this regard, inventory robot2300 retrieves two processing plates 2040 and places one plate onto eachextractor 2240 a-b so that extraction tubes 2044 of each plate 2040 arereceived by heater elements 2248 of the respective extractor 2240 a-b.Inventory robot 2300 also retrieves a first dry reagent plate 2050 a andliquid reagent plate 2060 and places them at dry reagent station 2220and liquid reagent station 2230, respectively. Typically, the liquid anddry reagent plates 2050, 2060 provide reagents for more than the numberof samples carried by a shuttle 2030. So the analyzer 2000 may not stagereagent plates each time a shuttle 2030 is placed into the analyzer.Additionally, inventory robot 2300 retrieves an amplification cartridge2070 from inventory deck 2014 by engaging notches 2072 via secondengagement features 2364. Amplification cartridge 2070 is placed atamplification cartridge station 2250 so that inlet openings 2073 arepositioned adjacent extractor 2240 a.

Thereafter, multichannel pipettor 2440 retrieves a first pipette tip2020 a, one tip for each of the three pipette assemblies 2470 a-c. Analiquot is retrieved 2607 from each of the sample containers 03 bypiercing the samples containers' penetrable seals 09 with the pipettetips 2020 and aspirating the sample therein. The aliquots are aspiratedinto respective extraction tubes 2044 of processing plate 2040. Aftereach mixing tube 2044 is inoculated with the aliquot, multichannelpipettor 2440 inserts pipette tip 2020 a into an adjacent tip holdingstation 2047 for later use. This is performed until an aliquot isextracted from each container 03. In the event there is a malfunctionsuch that an aliquot could not be retrieved, such as due to the seal notpiercing, analyzer 2000 retains that information in its memory 2514 soit can be communicated to pre-analytical system 10 which willappropriately organize the defective samples as is discussed in the '349Application.

Step 5: Return Sample Container Shuttle & Retrieve Another

Once an aliquot is retrieved from each sample container 03 in shuttle2030, analyzer 2000 communicates to workflow computing device 2540 thatit is going to return 2608 shuttle 2030 to pre-analytical system 10.Workflow computing device 2540 relays this communication topre-analytical system 10 which moves another shuttle 2030 containing theother half of the batch to shuttle transport assembly 300. Withinanalyzer 2000, clamping assembly 2212 releases shuttle 2030 andinventory robot 2300 returns shuttle 2030 containing used containers 03back to pre-analytical system 10 by placing shuttle 2030 into a returnlane of shuttle transport assembly 300. Inventory robot 2300 thenengages and moves 2610 the second shuttle 2030 of the batch andtransports it to shuttle retention assembly 2210 where it is retainedand the remaining aliquots of the batch are aspirated. Once aliquots aretransferred to the remaining extraction tubes 2044 of processing plates2040, shuttle 2030 is once again returned to pre-analytical system 10via inventory robot 2300.

In some embodiments a dual lane assay may be performed by analyzer 2000in which an aliquot from each sample container 03 is aspirated into twoextraction tubes 2044 rather than one. In such embodiment, a singleshuttle 2030 of twelve sample containers 03 would fill two processingplates 2040 each having 12 extraction tubes 2044. Thus, in thisembodiment, inventory robot 2300 only retrieves one shuttle 2030 for theassay and does not retrieve any further shuttles 2030.

Step 6: Process Samples

With processing plates 2040 inoculated with aliquots of sample, analyzer2000 processes 2612 the samples. The procedure is generally the sameregardless of the assay. The differences are not so much in method butin the reagents utilized. Thus, processing modules 2200 are capable ofperforming a wide array of assays. Processing generally includesextraction, isolation and amplification of an analyte, such as a DNAtarget.

Extraction involves reconstituting a dried lysis agent which may containmagnetic beads configured to bind to DNA. In this regard, multichannelpipettor 2440 picks up the previously used pipette tip 2020 a from thepipette tip holding station 2047 in processing plate 2040. Althoughmultichannel pipettor 2440 generally includes multiple pipetteassemblies 2470 a-c, a single pipette assembly 2470 can be driven alonga corresponding z-rail 2464 independently from the other pipetteassemblies 2470 in order to retrieve the previously used pipette tip2020 a from processing plate 2040. Once the tip 2020 a is retrieved,pipette assembly 2470 pierces the seal of a reconstitution buffer inliquid reagent plate 2060, retrieves an aliquot of the buffer, andtransfers it to dry reagent plate 2050 a where it pierces the seal overone of compartments 2044 and inoculates the compartment 2054 with thebuffer to rehydrate the lysis agent. The reconstituted lysis agent isthen aspirated and transferred to extraction tube 2044. This is repeateduntil all extraction tubes 2044 are inoculated with a lysis agent andmagnetic beads.

Extractors 2240 a-c then heat the extraction tubes 2044 and the contentstherein via heating elements 2248 in contact with extraction tubes 2044.While the mixture incubates, inventory robot 2300 removes first dryreagent plate 2050 from processing module 2200 and retrieves the seconddry reagent plate 2050 b from inventory deck 2014 and places it at dryreagent plate station 2220.

When incubation is complete, the motors 2244 of extractors 2240 a-b movepermanent magnets 2241 out of their respective housing 2242 and placesthem adjacent extraction tubes 2044 where the magnetic beads withextracted DNA attached thereto are drawn to the side of tube 2044.Multichannel pipettor 2440 then retrieves an aliquot of wash buffer fromreagent plate 2060 and rinses the tube mixtures. Magnets 2241 are movedback into their housing 2242 and the supernatant is removed from themixing tubes and discarded via liquid waste inlet which communicateswith a liquid waste bottle within inventory deck 2014. A neutralizationbuffer is transferred from liquid reagent plate 2060 to a mixing well2046 in processing plate 2040 adjacent extraction tubes 2044. Pipettor2440 then retrieves an elution buffer from liquid reagent plate 2040 anddispenses the elution buffer into extraction tubes 2044 to separate themagnetic beads from the isolated DNA. Magnets 2241 are moved back intoplace and the eluate is aspirated and transferred to mixing well 2046where it is mixed with the neutralization buffer. The neutralized sampleis then used to reconstitute the master mix within second dry reagentplate 2050 b. The mixture is then loaded into amplification cartridge2070 via multichannel pipettor 2440 and second pipette tips 2020 b whichinoculate cartridge 2070 by aspirating the mixture into inlet openings2073 of cartridge 2070. Amplification cartridge 2070 can receive theentire batch.

Step 7: Amplify/Analyze/Detect

Thereafter, end effector 2360 of inventory robot 2300 engages cartridge2070 and carries it to a detector 2270 associated with the processingmodule 2200. Inventory robot 2300 places cartridge 2070 onto platform2276 of thermocycler 2275 without significantly tipping cartridge 2070.This is possible at least because cartridge 2070 hangs from or iscarried so that it is positioned lower than fingers 2363 a-b of endeffector 2360. If fingers 2363 a-b were positioned lower than cartridge2070, cartridge 2070 may have to be dropped from end effector 2360.Motor 2278 then raises thermocycler 2275 to press cartridge 2070 againstreader 2271. Cartridge 2070 is then subjected to thermocycling so as toamplify the assay target. Reader 2271 detects 2614 for the presence ofthe assay target within the chambers 2075 of cartridge 2070.

Step 8: Discard & Repeat

Once detection is completed, the results are communicated to workflowcomputing device 2540. The used amplification cartridge 2070 is moved2616 via inventory robot 2300 to an amplification cartridge waste whichmay be in waste repository 2130 or elsewhere in analyzer 2000. Inventoryrobot 2300 also discards the used processing plates 2040 by stackingplates 2040 onto shelf 2138 of waste repository 2130. Dry and liquidreagent plates 2050, 2060 are placed back into their respectivecompartments within consumable repository 2110 for use in another assay.Dry and liquid reagent plates 2050, 2060 can generally be used in fourassay runs. Computing device 2510 keeps track of how many times a plate2050 or 2060 has been used and analyzer 2000 automatically discardsthese plates after their final run by placing the plates 2050, 2060 inwaste repository 2130. Once the consumables are discarded, theprocessing module 2200 can perform 2618 another assay.

Multiple Assays at Once

Each of processing modules 2200 can perform any assay on an assay menuat any given time provided appropriate consumables are inventoriedwithin its housing 2010. This allows analyzer 2000 to respond withflexibility to optimize throughput. For example, first processing module2200 a may have been performing a first assay for several runs. However,if there is a backlog of samples within pre-analytical system 10 thatrequire a second assay that is different from the first assay, firstprocessing module 2200 a can be used to assist in processing andanalyzing such samples by performing the second assay. This may be doneautomatically by analyzer 2000 without assistance from a user asanalyzer 2000 is in constant communication with pre-analytical system10.

Numerous variations, additions and combinations of the featuresdiscussed above can be utilized without departing from the presentinvention. For example FIGS. 17A-17C depict an analyzer 3000 accordingto another embodiment of the present disclosure. Analyzer 3000 issimilar to analyzer 2000 in that it includes a processing deck 3016having multiple processing modules 3200 a-c, an inventory robot 3300with a gripping end effector 3360, a liquid handling robot that includesmultiple multichannel pippetors 3440 a-c, a consumable storage area 3014and detectors 3270 a-c for detecting an analyte. In addition, analyzer3000 utilizes the same consumables as analyzer 2000, such as thepreviously described pipette tips 2020, shuttles 2030, processing plates2040, liquid reagent plates 2060, dry reagent plates 2050, andamplification cartridges 2070. However, analyzer 3000 differs withrespect to the arrangement of the consumable storage 3014 and detectors3270 a-c and with regard to certain consumable repositories.

In particular, analyzer 2000 includes a detection/analysis deck 2012that is located beneath an inventory deck 2014. However, analyzer 3000separates these decks horizontally rather than vertically. Thus,analyzer 3000 includes an inventory section 3014 and adetection/analysis section 3012. In the particular embodiment depicted,the inventory section 3014 is located at the left side of analyzer 300and detection/analysis section is located at the right side of analyzer3000.

Inventory section 3014 includes a first consumable repository 3110, asecond consumable repository 3120, and a waste repository 3130. Firstrepository 3110 is similar to repository 2110 in that they both receiveand store consumable items such as, reagent plates 2050 and 2060 andcartridges 2070. Second repository 3110 is located between firstrepository 3110 and waste repository 3130.

Second repository 3120, which is best shown in FIG. 18C, has verticalcompartments that are defined by walls 3122 and vertical rods/columnsdisposed opposite the walls 3122. These compartments are sized toreceive stacks of processing plates 2040. Rods 3124 help prevent thestacks of processing plates 2040 from falling over, while also allowingthe processing plates 2040 to be sufficiently exposed so that robot 2300can retrieve a plate 2040 from a respective stack.

Waste repository 3130 is generally the same as waste repository 2130.Waste repository 3130 demarcates a lateral boundary of inventory section3140 of analyzer 300 and helps separate the unused consumables anddetection/analysis section 3012, which can help isolate any potentialcontamination originating from either area.

Detection/analysis section 3012 includes a waste repository 3130 (in oneembodiment, the waste is amplification cartridges), a liquid wasterepository, 3170, and a plurality of detectors 3270. The wasterepository 3160 has an opening to receive and house waste, e.g., usedamplification cartridges 2070, until a user empties repository 3160.Amplified waste repository 3160 may be slidably attached to one or morerails for controlled movement into and out of analyzer 3000. Liquidwaste repository 3170 is connected to the processing deck 3016 via ahose or some other channeling device (not shown) so that liquid wastecan be disposed of from the processing deck 3016. Detectors 3270 a-c arethe same as detectors 2270 a-c and each include a thermocycler 3275 andreader head 3271. Detectors 3270 a-c are located in a verticalarrangement so that second detector 3270 b is located directly abovethird detector 3270 c, and first detector is located directly abovesecond detector 3270 b. Detectors 3270 a-c open in the same directionfor access by gripper 3360 of inventory robot 3300. In some embodiments,at least one detector 3270 may be located on the same horizontal planeas another detector and orthogonally arranged relative thereto.

FIGS. 18A-18C depict an analyzer 3000′ according to another embodimentof the present disclosure. Analyzer 3000′ is similar to analyzer 3000with the difference being that one or more consumable repositories aremoveable for ease of access. For example, as shown in FIG. 18B, secondconsumable repository 3120 may be moveable like a drawer so that a userhas access to each of the vertical compartments for replenishment ofprocessing plates 2040. In another example shown in FIG. 18C, first andsecond waste repositories 3110, 3120 may be positioned on a moveablebase 3144 so as to form a moveable consumable inventory 3142. In thisregard, base 3144 may be slidable on rails (not shown) so that bothfirst and second consumable repositories 3110, 3120 can be moved to aposition outside of system 3000′ for replenishment of consumables. In afurther example, a carousel consumable inventory (not shown) may includea plurality of compartments that are rotatable about a vertical axis.Such carousel inventory may be rotated to expose its compartments to auser for replenishment while also allowing consumables stored therein tobe positioned for access by robot 3300.

Analyzer 3000′ also includes a housing 3010 which includes apertures3012 in a front face thereof so that the various repositories can bemoved or removed, such as first and second repositories 3110, 3120,solid waste repository 3130, liquid waste repository 3170, and amplifiedwaste repository 3160, as shown in FIG. 18A. Doors 3014, which may behingedly connected to housing 3010, open to allow a user access to suchrepositories.

One example of an analyzer described herein includes: i) a housing; ii)a robotic arm comprising an end effector, the end effector having: a) abody rotatably connected to an articulating arm; and b) first and secondfingers coupled to the body and being moveable relative to each other ina first direction, each of the fingers having an engagement featureprojecting inwardly from each of the first and second fingers and towardthe other of the first and second fingers, the engagement feature beingconfigured to engage a recess of an article wherein the recess isconfigured to receive the engagement feature such that the robotic armcan carry the article that is suspended from the first and secondfingers when the engagement features are so engaged with the article.The analyzer also has: iii) at least one shuttle platform for receivinga shuttle carrying sample containers, the containers carrying sample tobe evaluated by the analyzer; where the shuttle platform has a jawassembly that automatically moves from an open position to a closedposition the jaw assembly comprising engagement members that do notcontact the bottom portion of the sample containers carried by theshuttle when the jaw assembly is in an open position and engages thebottom portion of the sample containers when the jaw assembly is in theclosed position. The analyzer can also have an automatic pipettor thataspirates sample from the sample containers and wherein the jaw assemblyof the shuttle platform is closed when the automatic pipettor aspiratessample from the sample containers. The robotic arm places the shuttle onthe shuttle platform when the jaw assembly of the shuttle platform is inthe open position. The automated analyzer may also have a magneticextractor. The magnetic extractor may include: i) a housing defining acavity; ii) adjacent rows of permanent magnets moveably disposed withinthe cavity of the housing; iii) a drive mechanism connected to the rowsof permanent magnets and configured to move the rows of permanentmagnets into and from the cavity; and iv) a plurality of heatingelements that extend from the housing in rows that are disposed atopposite sides of the cavity. Moving the magnets from the first positionto the second position disposes the rows of magnets directly betweenrows of the heating elements so that each permanent magnet aligns with arespective heating element. The magnetic extractor may also have a dripplate defining troughs that are each disposed adjacent to respectiverows of heating elements.

The magnetic extractor can be adapted to receive a processing platethereon, the heating elements each defining a recess configured toreceive and hold an extraction tube of the processing plate disposedabove the magnetic extractor, the heating elements being connected to apower source that heats the heating elements so that when the processingplate is placed over the heating elements, pipette tips held by theprocessing plate extend into the troughs of the drip plate. In operationof the analyzer the processing plate is placed on the magnetic extractorby the robotic arm. In some examples the robotic arm transports theprocessing plate onto the magnetic extractor by engaging the engagementfeatures of the robotic fingers with upwardly extending engagementmembers from the processing plate, wherein the upwardly extendingengagement members have openings that receive the engagement featureswhen the robotic fingers are in a first engagement position, wherein therobotic fingers are closer together in the first engagement positionthan in a second position in which the distance between the roboticfingers is too far apart for the engagement features to engage theengagement members. In some embodiments the robotic fingers have asecond engagement feature that extends downward from the roboticfingers. In one example the downward extending features from the roboticarms comprise a post with an inverted frustoconical projection extendingtherefrom. In operation, the inverted conical feature engages acorresponding notch in a consumable article that is transported from afirst location to a second location in the automated analyzer. Theautomated analyzer may further include a consumable repository forreceiving a consumable item for use in the automated analyzer. Examplesof consumable items include a processing plate, a dry reagent plate, aliquid reagent plate and an amplification cartridge. In some embodimentsthe robotic arm has a scanner wherein the robotic arm retrieves aconsumable stored in the consumable repository by reading a code on theconsumable using the scanner. In one example, the consumable repositoryreceives consumables from a first side and wherein robotic arm retrievesconsumables from a second side of the consumable repository. In oneexample, the analyzer has one or more processing modules, a processingmodule having the shuttle platform and the magnetic extractor. In theexample where the analyzer has multiple processing modules, two adjacentprocessing modules use one shuttle platform. In one example, aprocessing module has dry and liquid reagent stations adjacent themagnetic extractor, wherein the magnetic extractor is adapted to receivea processing plate thereon and wherein the processing plate ispositioned lower in the processing module relative to dry and liquidreagent plates placed at respective dry and liquid reagent stations.

In another aspect a processing plate for use in an automated diagnosticsystem includes: i) a plate body defining a plurality of extractiontubes, mixing wells, and pipette tip holding stations, the extractiontubes, mixing wells, and pipette tip holding stations each definingopenings that extend through an upper surface of the plate body; and ii)engagement members that extend vertically upward from the upper surfaceof the plate body having openings in the vertical portion of theengagement members, wherein the openings face the perimeter of the platebody, such openings being configured to receive an engagement feature ofan automated transport device. In one example, the processing plate anupper surface, a lower surface and an edge, the edge extending betweenthe upper and lower surfaces and defining a perimeter of the plate body.In another example a processing plate for use in an automated diagnosticsystem includes: i) a plate body having an upper surface, a lowersurface and an edge, the edge extending between the upper and lowersurfaces and defining a perimeter of the plate body; and ii) a pluralityof sets of openings in the upper surface of the plate body and extendingtherethrough, wherein the openings terminate in a closed end. Forexample, each set has: i) an extraction tube having a tube body thatextends from the bottom surface and defines tube openings extendingthrough the upper surface; a well; and a pipette station that isconfigured to receive and hold a pipette tip. In one example each set ofextraction tube, well, and pipette station is aligned in a row and thepipette station is positioned closest to the edge on at least one sideof the plate body with the extraction tube and well further away fromthe perimeter of the processing plate.

In one example the engagement members that extend vertically upward fromthe upper surface of the plate body and that have openings in thevertical portion of the engagement members wherein the openings face theperimeter of the plate body, such openings being configured to receivean engagement feature of an automated transport device.

Also described herein is an inventory robot having a robotic arm with anend effector for carrying an article, the end effector having: i) a bodyrotatably connected to an articulating arm; and ii) at least two fingerscoupled to the body and extending therefrom, one of the at least twofingers being moveable relative to the other one of the at least twofingers. Each of the at least two fingers has a first projectionextending in a first direction toward the other of the at least twofingers for engaging a respective recess of the article. The respectiverecesses are configured to receive one of the projections each of the atleast two fingers that have a second projection extending in a downwarddirection relative to the first direction. The second projections arefor engaging a recess in the top of an article wherein the recess isconfigured to receive the second projection.

Also described herein is an automated analyzer having a robotic arm withan end effector for carrying an article. The end effector includes: i) abody rotatably connected to an articulating arm; and ii) first andsecond fingers coupled to the body and extending therefrom in a firstdirection and being moveable relative to each other in a seconddirection transverse to the first direction, each of the fingers havinga first engagement feature extending therefrom in the second directionand a second engagement feature extending downward from the first andsecond fingers, the second engagement feature being configured to engagea recess disposed in the top of an article wherein the recess isconfigured to receive the second engagement feature so as to suspend thearticle from the first and second fingers when the robotic arm carriesthe article from a first location to a second location.

Also described herein is an automated analyzer having: i) an inventoryrobot comprising a robotic arm with an end effector thereon, the endeffector comprising a body rotatably connected to an articulating arm;ii) a plurality of gripping fingers extending from the body from a firstside thereof wherein the body is rotatable on a vertical axis; iii) ascanner positioned on the end effector to be brought into proximity witharticles by the inventory robot, the inventory robot scans identifyinginformation disposed on an article and located on the end effector at aposition other than the location from which the gripping fingers extend.The analyzer also has a magnetic extractor having: i) a housing defininga cavity; ii) adjacent rows of permanent magnets moveably disposedwithin the cavity of the housing; iii) a drive mechanism connected tothe rows of permanent magnets and configured to move the rows ofpermanent magnets into and from the cavity; and iv) a plurality ofheating elements that extend from the housing in rows that are disposedat opposite sides of the cavity, the heating elements each defining arecess configured to receive and hold an extraction tube of a processingplate disposed above the magnetic extractor, the heating elements beingconnected to a power source that heats the heating elements. Inoperation, moving the magnets from the first position to the secondposition disposes the rows of magnets directly between rows of theheating elements so that each permanent magnet aligns with a respectiveheating element. The magnetic extractor also has a plurality of heatingelements extending from the housing; a drip plate defining troughs thatare each disposed adjacent to respective rows of heating elements; and aconsumable repository adapted to receive a consumable processing plate,the processing plate comprising a machine readable label thereon,wherein the processing plate is placed in the consumable repository froma first side and the machine readable label on the consumable is readfrom a second side of the consumable repository by the inventory robotscanner. In one example, the inventory robot is moved to the consumablerepository to obtain a processing plate and scans labels on articles inthe consumable repository and, when it identifies the consumable to beretrieved, removes the consumable from the consumable repository andplaces it on the magnetic extractor such that pipette tips held by theprocessing plate extend into the troughs of the drip plate.

Also described herein is a method of operating an automated analyzer ofbiological samples that includes: i) placing a shuttle rack carryingsample containers for analysis at a location adjacent to the analyzerhousing; ii) moving a robotic arm comprising an end effector such thatthe end effector translates to a position adjacent the analyzer whilethe other portions of the robot remain in the analyzer; iii) advancingthe first and second fingers toward the rack shuttle such that theengagement features of the first and second fingers enter correspondingslots in the rack shuttle wherein the distance between the slots in therack corresponds to the distance between the fingers extending from thebody when the fingers are inserted in the slots; iv) once the engagementmembers are advanced into the slots, translating the fingers of therobotic arm closer together to grasp the shuttle rack located within thepre-analytical system; and v) moving the shuttle rack from the positionadjacent the analyzer into the analyzer using the robotic arm. In oneexample, the end effector has a body with first and second fingersextending therefrom, each finger having an engagement feature thereonwherein the first and second fingers are disposed in a channel in thebody and can be translated closer together or further apart by therobot. In one example there is physical access between the analyzer andan adjacent pre-analytical system in which the samples were prepared foranalysis, the analysis to occur in the analyzer, and the robotic armretrieves the shuttle rack from the adjacent pre-analytical system andcarries it into the analyzer. The method can also include: i) using therobotic arm, placing the shuttle rack carried into the analyzer onto ashuttle retraining platform wherein the shuttle retaining platform has ajaw assembly with an open position and a closed position, wherein thejaw assembly is in the open position when the shuttle rack is placed onthe shuttle retaining platform; ii) releasing the tension between thegripping fingers and the shuttle rack and withdrawing the grippingfingers extending from the end effector from the slots in the shuttlerack; iii) after the gripping fingers have been withdrawn, moving thejaw assembly to the closed position, thereby causing engagement membersof the jaw assembly to secure against a lower portion of the samplecontainers in the shuttle when the jaw assembly is in the closedposition; iv) inserting a pipette tip into the sample container using arobotic pipettor; v) aspirating at least a portion of the sample in thesample container using the robotic pipettor; and vi) withdrawing thepipette tip from the sample container while the jaw assembly is in theclosed position. After withdrawing the pipette tip from the samplecontainer, the jaw is moved to the open position and the methodcontinues by: vii) advancing the first and second fingers of the endeffector toward the shuttle rack such that the engagement features ofthe first and second fingers enter corresponding slots in the shuttlerack wherein the distance between the slots in the shuttle rackcorresponds to the distance between the fingers extending from the bodywhen the fingers are inserted in the slots; viii) after the engagementmembers are advanced into the slots, translating the fingers closertogether to grasp the shuttle rack located within the pre-analyticalsystem; ix) transporting the shuttle rack from the shuttle retainingplatform back to the location adjacent the analyzer; x) releasing theshuttle rack from the end effector; and xi) retracting the end effectorback in to the analyzer.

In another example a method of operating an automated analyzer ofbiological samples includes the steps of: i) moving an end effector of arobotic arm of an inventory robot above an article positioned at a firstlocation, the end effector having a body with first and second fingerslocated in a channel and linearly movable within the channel, thefingers having engagement features thereon, to a location above anarticle positioned at a first location; ii) translating the first andsecond fingers apart so that the distance between them is greater than adistance between engagement members that are projections that extendupwardly from a body of the article, the engagement members beingdisposed inboard relative to a perimeter of the article and havingopenings facing the perimeter of the article; iii) moving the endeffector so that engagement features extending from each of the fingersalign with corresponding openings within the engagement members; iv)moving the first and second fingers toward each other so as to engagethe engagement member openings; v) lifting the article so that the bodyof the article is disposed beneath the fingers; and vi) moving thearticle to a second location.

In a further example the engagement features are one of first engagementfeatures projecting inwardly from each of the first and second fingersand toward the other of the first and second fingers or secondengagement features that extend downward from each of the fingerswherein the downward extending features from the fingers comprise a postwith an inverted frustoconical projection extending therefrom. In afurther example the first location is a consumable repository. Theconsumable repository may contain a first article comprising anengagement member in the top surface thereof. This exemplary method mayfurther include vii) moving the end effector over the top surface of thefirst article; and viii) lowering the end effector over the top surfaceof the article such that the second engagement features engage withcorresponding engagement members in the top surface of the firstarticle. The consumable repository may also contain a second articlecomprising a plurality of sets of openings in the upper surface of abody of the article and extending therethrough, wherein the openingsterminate in a closed end wherein each set has one each of: a) anextraction tube having a tube body that extends from the bottom surfaceand defines tube openings extending through the upper surface; b) awell; c) a pipette station that and configured receive and hold apipette tip, wherein each set of extraction tube, well, and pipettestation is aligned in a row wherein the pipette station is positionedclosest to the edge on at least one side of the plate body with theextraction tube and well further away from the perimeter of theprocessing plate; and d) engagement members inboard on the top surfaceand extending from the top surface thereof the engagement members havingopenings that face the perimeter of the top surface the method furthercomprising moving the end effector over the top surface of the firstarticle. The method can include the steps of: ix) aligning engagementfeatures of the end effector with the engagement members; and x)inserting the engagement features in the engagement members; xi)translating the first and second fingers closer together to grip theengagement members; and xii) carrying the second article to a secondlocation.

In one example the end effector is advanced horizontally to move thefingers into the corresponding recesses. In the embodiments wherein theend effector comprises a scanner, the method further comprises: i)instructing an inventory robot to retrieve an article from theconsumable repository; ii) scanning a machine readable label on thearticle in the consumable repository; iii) determining if the labelinformation matches an article that the inventory robot is instructed toretrieve; and iv) if a match is determined, engaging the arms of the endeffector with engagement members on the article and transporting thearticle from the consumable repository to a second location using theinventory robot.

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It is therefore to be understood that numerousmodifications may be made to the illustrative embodiments and that otherarrangements may be devised without departing from the spirit and scopeof the present invention as defined by the appended claims.

The invention claimed is:
 1. A sample processing system comprising: ahousing; a robotic arm comprising an end effector, the end effectorcomprising: a body rotatably connected to an articulating arm; and firstand second fingers coupled to the body and being moveable relative toeach other in a first direction, each of the first and second fingershaving an engagement feature projecting inwardly from each of the firstand second fingers and toward the other of the first and second fingers,the engagement feature being configured to engage with an article suchthat the robotic arm can carry and suspend the article from the firstand second fingers when the engagement features are so engaged with thearticle; and at least one platform configured to receive a shuttleadapted to carry a plurality of sample containers, each sample containerbeing received into a corresponding receptacle in the shuttle, whereineach of the plurality of sample containers comprise an open end that isadapted to receive a cap, a closed end, and a skirt at the closed endand wherein each of the plurality of sample containers carries sample tobe processed by the system, the at least one platform comprising aclamping assembly that receives the shuttle and automatically moves froman open position to a closed position, the clamping assembly comprisinga plurality of engagement members configured to not contact the skirt ofeach of the plurality of sample containers carried by the shuttle whenthe clamping assembly is in the open position and configured to extendthrough a corresponding plurality of transverse openings defined in eachreceptacle of the shuttle and penetrate into the skirt of the pluralityof sample containers to retain the plurality of sample containers in theshuttle when the clamping assembly is in the closed position.
 2. Thesystem of claim 1, further comprising an automatic pipettor thataspirates sample from the a sample container of the plurality of samplecontainers carried by the shuttle, and wherein the clamping assembly ofthe platform is closed when the automatic pipettor aspirates sample fromthe sample of the plurality of sample containers.
 3. The system of claim2, wherein the robotic arm places the shuttle on the platform when theclamping assembly of the platform is in the open position.
 4. The systemof claim 3, further comprising a magnetic extractor.
 5. The system ofclaim 4, wherein the magnetic extractor further comprises: a housingdefining a cavity; adjacent rows of permanent magnets moveably disposedwithin the cavity of the housing; a drive mechanism connected to therows of permanent magnets and configured to move the rows of permanentmagnets into and from the cavity; and a plurality of heating elementsthat extend from the housing in rows that are disposed at opposite sidesof the cavity; wherein moving the permanent magnets from a firstposition to a second position disposes the rows of permanent magnetsdirectly between rows of the heating elements so that each permanentmagnet aligns with a respective heating element; and a drip platedefining troughs that are each disposed adjacent to respective rows ofheating elements.
 6. The system of claim 4, wherein the magneticextractor is adapted to receive a processing plate thereon, wherein theplurality of heating elements each define a recess configured to receiveand hold an extraction tube of the processing plate disposed above themagnetic extractor, and wherein the troughs of the drip plate areconfigured to receive pipette tips held by the processing plate.
 7. Thesystem of claim 6, wherein the processing plate is placed on themagnetic extractor by the robotic arm.
 8. The system of claim 7, whereinthe robotic arm transports the processing plate onto the magneticextractor by engaging the engagement features of the first and secondfingers of the robotic arm with upwardly extending engagement membersfrom the processing plate, wherein the upwardly extending engagementmembers have openings that receive the engagement features when thefirst and second fingers of the robotic arm are in a first engagementposition, and wherein the robotic arm fingers are closer together in thefirst engagement position than in a second position in which a distancebetween the robotic arm fingers is too far apart for the engagementfeatures to engage the engagement members.
 9. The system of claim 1,wherein the first and second fingers of the robotic arm have a secondengagement feature that extends downward from the first and secondfingers of the robotic arm.
 10. The system of claim 9, wherein thesecond engagement features comprise a post with an invertedfrustoconical projection extending therefrom.
 11. The system of claim10, wherein the inverted frustoconical projection engages acorresponding notch in a consumable article that is transported from afirst location to a second location in the system.
 12. The system ofclaim 1, further comprising a consumable repository for receiving aconsumable item for use in the system.
 13. The system of claim 12,wherein the consumable items are selected from the group consisting of aprocessing plate, a dry reagent plate, a liquid reagent plate and anamplification cartridge.
 14. The system of claim 13, wherein the roboticarm further comprises a scanner, wherein the robotic arm retrieves aconsumable stored in the consumable repository by reading a code on theconsumable using the scanner.
 15. The system of claim 12, wherein theconsumable repository receives consumables from a first side, andwherein the robotic arm retrieves consumables from a second side of theconsumable repository.
 16. The system of claim 1, wherein a processingmodule in the system comprises the platform and a magnetic extractor.17. The system of claim 1, further comprising a plurality of processingmodules, wherein two adjacent processing modules use one platform. 18.The system of claim 16, wherein a processing module further comprisesdry and liquid reagent stations adjacent the magnetic extractor, whereinthe magnetic extractor is adapted to receive a processing plate thereon,and wherein the processing plate is positioned lower in the processingmodule relative to dry and liquid reagent plates placed at respectivedry and liquid reagent stations.